Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative...

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Applied nutritional investigation Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: A prospective study Ibrahim Sari, M.D. a, *, Yasemin Baltaci, M.D. b , Cahit Bagci, M.D. b , Vedat Davutoglu, M.D. a , Ozcan Erel, M.D. c , Hakim Celik, M.D. c , Orhan Ozer, M.D. a , Nur Aksoy, M.D. d , and Mehmet Aksoy, M.D. a a Cardiology Department, Gaziantep University, School of Medicine, Gaziantep, Turkey b Physiology Department, Gaziantep University, School of Medicine, Gaziantep, Turkey c Biochemistry Department, Harran University, School of Medicine, Sanliurfa, Turkey d Biochemistry Department, Gaziantep University, School of Medicine, Gaziantep, Turkey Manuscript received December 15, 2008; accepted May 30, 2009. Abstract Objective: Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. Methods: A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21–24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting z20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. Results: Compared with the Mediterranean diet, the pistachio diet decreased glucose (P < 0.001, 8.8 6 8.5%), low-density lipoprotein (P < 0.001, 23.2 6 11.9%), total cholesterol (P < 0.001, 21.2 6 9.9%), and triacylglycerol (P ¼ 0.008, 13.8 6 33.8%) significantly and high-density lipoprotein (P ¼ 0.069, 3.1 6 11.7%) non-significantly. Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P < 0.001 for both). The pistachio diet significantly improved endothelium-dependent vasodilation (P ¼ 0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (P < 0.001 for all), whereas there was no significant change in C-reactive protein and tumor necrosis factor-a levels. Conclusion: In this trial, we demonstrated that a pistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Ó 2010 Published by Elsevier Inc. Keywords: Pistachio; Endothelium; Lipid; Inflammation; Oxidation Introduction Epidemiologic studies have shown that frequent nut consumption decreases the risk of coronary heart disease (CHD). Compared with people who consumed nuts less than one time per week, people who ate nuts at least five times per week showed a 50% reduction in risk [1–4]. Nuts are rich in monounsaturated fatty acid (MUFA) and polyun- saturated fatty acid (PUFA), which are known to have favor- able effects on the lipid profile [5]. However, the potential benefits of the nuts on decreasing CHD are not limited to their effects on lipid parameters. Nuts are also a good source of Financial support of the present study was provided by the Pistachio Investigation Group of the Gaziantep Chamber of Commerce. *Corresponding author. Tel.: 90-342-360-6060; fax: 90-342-360-3928. E-mail address: [email protected] (I. Sari). 0899-9007/10/$ – see front matter Ó 2010 Published by Elsevier Inc. doi:10.1016/j.nut.2009.05.023 Nutrition 26 (2010) 399–404 www.nutritionjrnl.com

Transcript of Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative...

Nutrition 26 (2010) 399–404

Applied nutritional investigation

Effect of pistachio diet on lipid parameters, endothelial function,

inflammation, and oxidative status: A prospective study

Ibrahim Sari, M.D.a,*, Yasemin Baltaci, M.D.b, Cahit Bagci, M.D.b, Vedat Davutoglu, M.D.a,Ozcan Erel, M.D.c, Hakim Celik, M.D.c, Orhan Ozer, M.D.a, Nur Aksoy, M.D.d,

and Mehmet Aksoy, M.D.a

aCardiology Department, Gaziantep University, School of Medicine, Gaziantep, TurkeybPhysiology Department, Gaziantep University, School of Medicine, Gaziantep, TurkeycBiochemistry Department, Harran University, School of Medicine, Sanliurfa, Turkey

dBiochemistry Department, Gaziantep University, School of Medicine, Gaziantep, Turkey

Manuscript received December 15, 2008; accepted May 30, 2009.

Abstract Objective: Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We

www.nutritionjrnl.com

Financial support

Investigation Group o

*Corresponding au

E-mail address: dr

0899-9007/10/$ – see

doi:10.1016/j.nut.2009

aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters,

endothelial function, inflammation, and oxidation in healthy young men living in a controlled

environment.

Methods: A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean

age 22 y, range 21–24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean

diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting

z20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements

were performed at baseline and after each diet.

Results: Compared with the Mediterranean diet, the pistachio diet decreased glucose (P< 0.001,

�8.8 6 8.5%), low-density lipoprotein (P< 0.001, �23.2 6 11.9%), total cholesterol (P< 0.001,

�21.2 6 9.9%), and triacylglycerol (P¼ 0.008, �13.8 6 33.8%) significantly and high-density

lipoprotein (P¼ 0.069, �3.1 6 11.7%) non-significantly. Total cholesterol/high-density lipoprotein

and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P< 0.001 for

both). The pistachio diet significantly improved endothelium-dependent vasodilation (P¼ 0.002,

30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and

malondialdehyde and increased superoxide dismutase (P< 0.001 for all), whereas there was no

significant change in C-reactive protein and tumor necrosis factor-a levels.

Conclusion: In this trial, we demonstrated that a pistachio diet improved blood glucose level,

endothelial function, and some indices of inflammation and oxidative status in healthy young men.

These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable

effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies.

� 2010 Published by Elsevier Inc.

Keywords: Pistachio; Endothelium; Lipid; Inflammation; Oxidation

Introduction

Epidemiologic studies have shown that frequent nut

consumption decreases the risk of coronary heart disease

of the present study was provided by the Pistachio

f the Gaziantep Chamber of Commerce.

thor. Tel.: 90-342-360-6060; fax: 90-342-360-3928.

[email protected] (I. Sari).

front matter � 2010 Published by Elsevier Inc.

.05.023

(CHD). Compared with people who consumed nuts less

than one time per week, people who ate nuts at least five

times per week showed a 50% reduction in risk [1–4]. Nuts

are rich in monounsaturated fatty acid (MUFA) and polyun-

saturated fatty acid (PUFA), which are known to have favor-

able effects on the lipid profile [5]. However, the potential

benefits of the nuts on decreasing CHD are not limited to their

effects on lipid parameters. Nuts are also a good source of

I. Sari et al. / Nutrition 26 (2010) 399–404400

dietary fiber, vitamins, micronutrients, antioxidants, amino

acids (e.g., arginine), and plant stenols [5].

The majority of the nut studies were performed with wal-

nuts, almonds, and peanuts. Thus far, to our knowledge,

only three studies have been conducted in humans investigat-

ing the effects of pistachio nuts, which were performed as out-

patient dietary intervention trials [6–8]. Investigators are more

focused on the favorable effects of nuts beyond their effects on

lipid parameters. Endothelial dysfunction is an early key event

in the atherosclerotic process that predicts future CHD devel-

opment [9,10]. Endothelial function measurement can be

non-invasively performed. A recent study has demonstrated

that substituting walnuts for MUFA in a Mediterranean diet

improved endothelium-dependent vasodilation (EDV) in hy-

percholesterolemic subjects as a measurement of endothelial

function [11]. Like the walnut, the pistachio is a good source

of L-arginine, which is a precursor of endogenous vasodilator

nitric oxide. To our knowledge, there are as yet no data regard-

ing the effect of a pistachio diet on endothelial function.

Inflammation and oxidation play an important role in the

pathogenesis and progression of CHD. Some studies have

shown that nuts have favorable effects on inflammation and

oxidative status; however, our knowledge about the impact

of pistachios on inflammatory and oxidative balance is

limited. In this study we therefore investigated the effect of

an Antep pistachio (Pistacia vera L.) diet on lipid parameters,

endothelial function, inflammation, and oxidative status in

healthy young men living in a controlled environment, which

has not been studied previously.

Table 1

Protocol description in summary

Weight, blood pressure,

laboratory and endothelial

function measurements

/ 33 healthy young men living in

a controlled environment

Mediterranean diet

Y 4 wk

Weight, blood pressure,

laboratory and endothelial

function measurements

/ Pistachio was added to the

Mediterranean diet by

replacing 32% of energy

obtained by monounsaturated

fatty acid

Y 4 wk

Weight, blood pressure,

laboratory and endothelial

function measurements

/ 32 participants finished the

protocol

Materials and methods

Study population

To our knowledge, previous nut studies were organized as

outpatient dietary modification studies. Although all of the

previously published studies have reported good compliance

of the participants to the administered diet, we believe that

subjects living in a controlled environment would provide

a better sample population in a dietary intervention study.

After providing the required legal permissions, we performed

the study in the vocational police education school of Gazian-

tep, Turkey. In the vocational police education school of

Gaziantep, all students were living in a controlled environ-

ment and eating in the same place. Sleeping and waking

hours and daily activities of the students were similar. They

were not allowed to go outside the school borders and they

were not provided any additional food other than that served

during meal times, except unlimited water.

Thirty-three healthy students (mean age 22 y, range

21–24) were included in the study. All enrolled subjects

were free of acute or chronic medical disorders and were of

normal body habitus. All subjects underwent a detailed

medical history and physical examination by the investigator

physicians. Exclusion criteria were smoking any amount,

history of eating nuts frequently (more than once a week),

a history of a food or nut allergy, regular use of any drugs

including vitamin supplements, and a history of any known

disease. Subjects with concomitant inflammatory diseases

such as infections, recent surgical procedures, or dyslipide-

mia were also excluded from the study. Participants were

requested to abstain from coffee products and alcohol

consumption during the recruitment period. The study proto-

col was approved by the ethical committee of Gaziantep

University and all participants gave informed consent.

Participants were offered free pistachios but no monetary

compensation.

Protocol

Before the study, students were eating the same kind of

regular diet (total energy from protein 20%, carbohydrate

47%, and fat 33%) prepared in the school kitchen. Although

they were eating the same kind of food, the amount was not

standardized for each student. They were allowed to eat as

much as they wanted if the food remained. To overcome

the disparities across the food intakes of the participants

(amount, calories, proportions of protein, fat, carbohydrate,

etc.), we accepted the recruitment period as a run-in period.

A Mediterranean-type diet was administered for 4 wk. After

4 wk, the participants continued to receive the Mediterra-

nean-type diet but pistachio was added by replacing the

MUFA content constituting z20% of daily caloric intake.

Because diet-induced lipoprotein changes stabilize in less

than 4 wk, we planned the diet periods as 4 wk [12]. The

protocol description was summarized in Table 1.

The Mediterranean-type diet was composed of natural

food stuff. It was rich in vegetable and fish, whereas red

meat, fat products, and egg products were limited. The pista-

chio diet was similar to the Mediterranean-type diet, but

pistachio partly replaced MUFA-rich foods. Prepackaged,

roasted unsalted pistachios (60 to 100 g) were administered

as an appetizer during the second 4-wk period. In the pistachio

diet, pistachio contributed z20% of total energy and replaced

32% of the energy obtained from MUFAs in the control diet

I. Sari et al. / Nutrition 26 (2010) 399–404 401

(Table 2). The pistachio diet was equivalent to the Mediterra-

nean diet in total calory intake and proportions of carbohy-

drate and protein intakes; however, saturated fatty acid and

PUFA intakes were lower (P¼ 0.02 and P< 0.001, respec-

tively) and MUFA and fiber intakes were higher (P< 0.001

and P< 0.001, respectively). According to the data provided

by the Pistachio Investigation Institute, Gaziantep, the com-

position of 100 g of pistachio was 18.3 g of protein, 52.7 g

of fat (saturated fatty acid 6.7 g, MUFA 36.2 g, and PUFA

9.8 g), 20 g of carbohydrate, and 7.4 g of fiber.

During the study period a registered dietitian supervised

mealtimes and ensured the complete intake of the respective

meals. The components of the food during the study period

were prepared and served by a food company (Tam Sofra

Inc., Gaziantep, Turkey) under the supervision of the regis-

tered dietitian. The participants ate their breakfast, lunch,

and dinner in the same field. Leftover foodstuffs were

collected and weighed by the dietitian to determine compli-

ance. Any deviations from the study protocol were recorded

and reviewed by the investigators during the study.

Fasting blood sample collection, endothelial function,

body weight, and blood pressure measurements were

performed three times (during the run-in period, after 4 wk

[4 wk after the Mediterranean-type diet], and after 8 wk

[4 wk after pistachio diet administration]). Because the

school program and the activities of the participants were pre-

planned for the entire education year, there was no change in

daily activities of the participants during the study period.

Endothelial function measurement

Endothelial function measurements were performed by the

same examiner who was unaware of the stage of the study.

Each subject was studied in the morning hours (08:00 to

10:00) after fasting >8 h before the examination. Studies

were performed in a quiet, semi-dark, temperature-controlled

room (20–25 �C) with the subject lying in a supine position.

Images were obtained using a commercially available device

(Vivid 7, GE Vingmed Ultrasound AS, Horten, Norway) with

a 12-MHz linear array transducer. According to the power cal-

culation, to provide 80% power at 5% significance to detect

Table 2

Comparison of nutritional status of subjects during the Mediterranean and

pistachio diets

Variable Mediterranean diet Pistachio diet P

Total calories (kcal/d) 1966 6 224 1983 6 241 >0.1

CHO (% energy) 48.7 6 3.2 49.2 6 2.8 >0.1

Protein (% energy) 17.1 6 1.5 16.8 6 1.7 >0.1

Fat (% energy) 33.5 6 2.2 33.1 6 1.9 >0.1

SFA 5.9 6 1.1 4.8 6 1.4 0.02

MUFA 13.3 6 1.6 20.2 6 2.3 <0.001

PUFA 14.2 6 1.3 7.1 6 1.0 <0.001

Fiber (g) 6.4 6 2.1 11.3 6 2.4 <0.001

CHO, carbohydrate; MUFA, monounsaturated fatty acid; PUFA, polyun-

saturated fatty acid; SFA, saturated fatty acid.

a 2% mean absolute difference in EDV and endothelium-

independent vasodilation as significant, 25 subjects would

need to complete the study.

The measurements were performed as previously

described [13]. The brachial artery was imaged longitudi-

nally, 2 to 5 cm above the antecubital crease. An occluding

cuff placed proximally on the forearm was inflated to a pres-

sure of 200 mmHg for 5 min and rapidly deflated to induce

reactive hyperemia. Brachial artery scans were obtained 30

s before cuff inflation (first baseline), at 60 to 90 s after

cuff deflation to assess EDV, after a 10-min rest (second

baseline), and 3 min after 0.4 mg of sublingual glyceryl trini-

trate to evaluate endothelium-independent vasodilation.

Arterial diameter was measured with ultrasonic calipers at

end diastole, incident with the R wave on the electrocardio-

gram. Three cardiac cycles were analyzed for each scan,

and measurements were averaged. Reliability of the measure-

ments was qualified by having them remeasure a random

sample of 15 subjects.

Laboratory measurements

Venous blood samples of the participants were collected

from the antecubital vein while patients rested in a supine

position after an overnight fast. Serum and ethylenediaminete-

tra-acetic acid plasma samples were stored at�80 �C and an-

alyzed at the end of the study period. Total cholesterol (TC),

high-density lipoprotein (HDL), and triacylglycerol (TG)

levels were determined by enzymatic–colorimetric methods.

Low-density lipoprotein (LDL) was calculated by the Friede-

wald formula. Oxidized LDL was calculated by a monoclonal

antibody–based immunoassay. Apolipoproteins (Apo) Al and

B were determined by turbidimetry. Homocysteine was deter-

mined by fluorescence polarization immunoassay.

High-sensitivity C-reactive protein (hs-CRP) was mea-

sured by chemiluminescent immunometric assay. Interleu-

kin-6 and tumor necrosis factor-a were determined by

enzyme-linked immunosorbent assay. Total oxidant status

(TOS) was determined as previously described [14]. Serum

lipid hydroperoxide level was determined by the ferrous

ion oxidation–xylenol orange method. Malondialdehyde

(MDA) was measured by a standard high-performance liquid

chromatographic method. Superoxide dismutase (SOD)

levels were performed by a commercially available SOD

kit. All laboratory analyses were done in duplicate.

Statistical analysis

Continuous variables are expressed as mean 6 standard

deviation and categorical data are expressed as percentages.

Two-tailed t test for paired samples was used to compare

changes in outcome variables in response to diets. The differ-

ences between the compositions of the Mediterranean and

pistachio diets were tested with unpaired t test or chi-square

test. Because hs-CRP was highly skewed, a logarithmic

transformation was used to obtain a normal distribution

I. Sari et al. / Nutrition 26 (2010) 399–404402

before analysis. Values were then transformed back and

reported in their original form for presentation. Two-tailed

P< 0.05 was considered statistically significant. All statisti-

cal studies were carried out with SPSS 11.5 (SPSS Inc.,

Chicago, IL, USA).

Results

Of the 33 participants initially included into the study,

1 subject had to undergo a urologic operation; therefore,

32 subjects (mean age 22 y, range 21–24) completed the pro-

tocol. Table 3 presents body weight, blood pressure, glucose,

and lipid parameters of the participants at baseline and at the

end of each diet. Body weight and blood pressure of the par-

ticipants remained unchanged during the study. Compared

with the Mediterranean diet, the pistachio diet caused signif-

icant decreases in glucose levels (P< 0.001, �8.8 6 8.5%).

Pistachio produced significant decreases in LDL (P< 0.001,

�23.2 6 11.9%), TC (P< 0.001, �21.2 6 9.9%), and TG

(P¼ 0.008, �13.8 6 33.8%) and a non-significant decrease

in HDL (P¼ 0.069, �3.1 6 11.7%; Fig. 1) when compared

with the Mediterranean diet. There were significant reduc-

tions in ApoA1 and ApoB levels and ratios of TC/HDL

and LDL/HDL (P< 0.001 for all), whereas oxidized LDL

and homocysteine levels and the ApoB/ApoA1 ratio re-

mained unchanged (Table 3).

Suitable brachial artery endothelial function measure-

ments were available for all 32 subjects who completed the

study. The pistachio diet produced significant improvement

in the EDV (P¼ 0.002, 30% relative increase), whereas

endothelium-independent vasodilation remained unchanged

when compared with the Mediterranean diet (Table 4, Fig. 2).

The pistachio diet caused significant decreases in serum in-

terleukin-6, TOS, lipid hydroperoxide, and MDA and an in-

crease in SOD (P< 0.001 for all), whereas there were no

significant changes in hs-CRP and tumor necrosis factor-

a levels when compared with the Mediterranean diet (Table 5).

Table 3

Body weight, blood pressure, glucose, and lipid parameters at baseline and at the

Variable Baseline Med

Weight (kg) 69.3 6 4.9 69

Systolic BP (mmHg) 117 6 8 11

Diastolic BP (mmHg) 73 6 8 7

Glucose (mg/dL) 91 6 8 9

TC (mg/dL) 199.6 6 41.8 190

TG (mg/dL) 91.2 6 39.7 112

HDL (mg/dL) 43.3 6 9.7 43

LDL (mg/dL) 142.0 6 37.4 124

Oxidized LDL (ng/mL) 355.1 6 109.9 331

TC/HDL 4.86 6 1.0 4.4

LDL/HDL 3.39 6 0.9 2.8

ApoA1 (g/L) 1.24 6 0.17 1.3

ApoB (g/L) 0.65 6 015 0.6

ApoB/ApoA1 0.53 6 0.15 0.4

Homocysteine (mmol/L) 10.7 6 3.2 10

Apo, apolipoprotein; BP, blood pressure; HDL, high-density lipoprotein; LDL,

Discussion

In this 8-wk dietary intervention trial, we demonstrated

that a pistachio diet had favorable effects on glucose level,

lipid parameters, endothelial function, and some indices of

inflammation and oxidative status in healthy young men.

Most of the nut studies were performed with walnuts,

almonds, and peanuts. Thus far, to our knowledge, only three

studies have been conducted in humans investigating the

effects of pistachio nuts, which were performed as outpatient

dietary intervention trials [6–8]. Therefore, we believe that

our study is unique in its design because it was conducted

in a population living in a controlled environment. Previous

studies about the effect of pistachio on lipid parameters have

shown favorable effects [6–8]. Edwards et al. [6] demon-

strated that 3 wk of a pistachio diet caused significant

decreases in TC, TC/HDL ratio, and LDL/HDL ratio and

a significant increase in HDL in moderately hypercholester-

olemic patients. TG and LDL levels remain unchanged.

Kocyigit et al. [7] reported that 3 wk of a pistachio diet caused

significant decreases in TC, TC/HDL ratio, and LDL/HDL

ratio and a significant increase in HDL in normolipidemic

healthy volunteers. TG and LDL levels remained unchanged.

Sheridan et al. [8] reported that 4 wk of a pistachio diet caused

significant decreases in TC/HDL ratio and LDL/HDL ratio

but a significant increase in HDL in subjects with moderate

hypercholesterolemia. TC, LDL, and TG remained un-

changed. In our study we demonstrated significant decreases

in glucose, TC, TG, LDL, TC/HDL ratio, and LDL/HDL

ratio in normolipidemic healthy young men. Although there

was a trend of a decrease in HDL level, it was not statistically

significant. The present study is the first demonstrating

a decrease in LDL and TG levels with a pistachio diet. In

addition, the three previous pistachio studies were associated

with an increase in HDL, whereas the present study showed

a non-significant decrease. One interesting result of the

present study is the significant decrease in blood glucose

end of each diet

iterranean diet Pistachio diet P

.7 6 5.0 69.5 6 5.1 >0.1

9 6 8 117 6 6 >0.1

4 6 7 73 6 7 >0.1

2 6 8 84 6 6 <0.001

.7 6 30.1 149.4 6 26.5 <0.001

.1 6 45.5 91.1 6 38.1 0.008

.5 6 9.2 41.7 6 7.38 0.069

.5 6 24.5 95.0 6 23.2 <0.001

.4 6 95.6 346.2 6 82.7 >0.1

0 6 0.8 3.78 6 0.7 <0.001

8 6 0.7 2.30 6 0.6 <0.001

4 6 0.18 1.20 6 0.20 <0.001

4 6 0.14 0.57 6 0.15 <0.001

9 6 0.13 0.48 6 0.14 >0.1

.6 6 3.8 11.0 6 3.7 >0.1

low-density lipoprotein; TC, total cholesterol; TG, triacylglycerol.

Fig. 1. A pistachio diet resulted in significant reductions in LDL

(* P< 0.001, �23.2 6 11.9%), TC (* P< 0.001, �21.2 6 9.9%), and TG

(** P¼ 0.008, �13.8 6 33.8%) and a non-significant reduction in HDL

(*** P¼ 0.069, �3.1 6 11.7%) when compared with the Mediterranean

diet. HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total

cholesterol; TG, triacylglycerol.

Table 4

Brachial endothelial function at baseline and at the end of each diet

Variable Baseline Mediterranean

diet

Pistachio

diet

P

Baseline artery

diameter (mm)

3.22 6 0.23 3.26 6 0.25 3.26 6 0.24 >0.1

EDV (%) 7.19 6 1.65 7.86 6 2.28 10.29 6 2.76 0.002

EIDV (%) 13.53 6 3.20 13.33 6 3.41 14.65 6 2.43 >0.1

EDV, endothelium-dependent vasodilation; EIDV, endothelium-indepen-

dent vasodilation.

Fig. 2. Endothelial-dependent vasodilation in brachial arteries of 32 men. A

pistachio diet produced a significant improvement in endothelial-dependent

vasodilation (30% relative increase) when compared with the Mediterranean

diet.

I. Sari et al. / Nutrition 26 (2010) 399–404 403

level with the pistachio diet, which warrants further studies

especially in the diabetic population.

It is known that a diet rich in MUFA has favorable effects

on CHD risk profile and pistachio is an excellent source of

MUFA [15,16]. Dietary fiber intake is associated with a lower

risk of CHD and fiber content was high in the pistachio diet

[17–19]. These might explain the favorable effects of pista-

chio on lipid parameters. Most nut studies were performed

based on an isoenergetic diet with a control group so that

nuts were replaced with MUFA content constituting

z15–20% of daily caloric intake. In our recent report, in

an experimental model of rats, consumption of pistachio as

20% of daily caloric intake had beneficial effects on lipid

parameters and LDL oxidation that were blunted when pista-

chio intake was increased to 40% of daily caloric intake [20].

Therefore, pistachio intake as 20% of daily caloric intake

seems reasonable. Blood pressure and body weight of the

participants did not change during the study and this was

compatible with the data of previous nut studies.

Although it has been documented that a pistachio diet has

favorable effects on lipid parameters, investigations have

found that their cardioprotective effect has some other mech-

anisms beyond their hypolipidemic effects. Endothelial

dysfunction is an early key event in the atherosclerotic

process that predicts future CHD development [9,10]. The

effect of pistachio on endothelial function has not been stud-

ied previously. In a recent study, substituting walnuts for

MUFA in a Mediterranean diet resulted in an improvement

in EDV in hypercholesterolemic adults [11]. In the present

study, we demonstrated that a pistachio diet resulted in an im-

provement in EDV in normolipidemic healthy young men

similar to a walnut diet. Although the specific mechanism

is unknown, several possible mechanisms can be proposed.

First, cholesterol lowering as in the present cohort is known

to improve endothelial function [21]. Second, the high

L-arginine content of pistachios might contribute to the

improvement in EDV, which is a precursor of endogenous

vasodilator nitric oxide [22]. Third, the favorable effects of

a pistachio diet on inflammatory and oxidative statuses,

which were demonstrated in the present study, and the fiber,

vitamin, micronutrient, and phytosterol content of pistachio

might improve EDV.

Inflammation and oxidation play an important role in the

pathogenesis and progression of atherosclerosis. To date,

there are no data about the effect of pistachio on inflammatory

parameters. A pistachio diet did not cause significant changes

in hs-CRP and tumor necrosis factor-a levels. However, there

was a significant decrease in interleukin-6 level, which is also

Table 5

Markers of inflammation and oxidation at baseline and at the end of each diet

Variable Baseline Mediterranean

diet

Pistachio

diet

P

hs-CRP (mg/dL)* 1.27 (0.90) 0.93 (0.34) 0.85 (0.72) >0.1

IL-6 (pg/mL) 1.44 6 1.02 1.14 6 0.66 0.79 6 0.65 <0.001

TNF-a (pg/mL) 8.6 6 6.0 8.4 6 5.6 9.0 6 5.7 >0.1

TOS (mmol H2O2

equivalent/L)

9.34 6 1.13 11.45 6 3.48 8.58 6 0.73 <0.001

LOOH (mmol/L) 6.33 6 0.60 7.85 6 1.88 5.48 6 0.56 <0.001

MDA (nmol/L) 64.4 6 3.9 75.9 6 15.8 58.6 6 4.5 <0.001

SOD (U/mL) 1.08 6 0.28 0.42 6 0.28 1.55 6 0.32 <0.001

hs-CRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; LOOH,

lipid hydroperoxide; MDA, malondialdehyde; SOD, superoxide dismutase;

TNF-a, tumor necrosis factor-a; TOS, total oxidant status.

* Median values are presented in parentheses. Data were logarithmically

transformed before analysis.

I. Sari et al. / Nutrition 26 (2010) 399–404404

an indicator of inflammation. In a recent paper, Kocyigit et al.

[7] reported that a 3-wk pistachio diet had a favorable effect on

oxidative stress. They found a decrease in MDA level and an

increase in antioxidant potential. In the present study we did

not find any difference in oxidized LDL level among diets;

however, the pistachio diet caused not only significant

decreases in lipid hydroperoxide and MDA levels, which

are indices of oxidation and lipid peroxidation, but also a sig-

nificant increase in SOD, which reflects antioxidant potential.

Moreover, we found a significant decrease in TOS with the

pistachio diet. Various components of oxidation and antioxi-

dation might be affected in different ways, but measuring

TOS rather than those individual variables might be more

practical. Therefore, a decrease in TOS after a pistachio diet

provides additional data that help us extend the beneficial

effects of pistachios beyond lipid lowering.

In conclusion, in this 8-wk dietary intervention trial, we

not only confirmed the previous findings about the beneficial

effects of a pistachio diet on lipid parameters but also demon-

strated that it caused improvements in blood glucose level,

endothelial function, and some indices of inflammation and

oxidative status in healthy young men living in a controlled

environment. These findings are in accordance with the

idea that nuts, in particular pistachio nuts, have favorable

effects beyond lipid lowering that need to be tested with

prospective follow-up studies.

Acknowledgments

The authors thank the subjects for participating and co-

operating during the study period. They also appreciate the

help of the administration of vocational police education

school of Gaziantep and the Gaziantep police department.

They appreciate the help of Nilgun Dogruer Kalkanci from

the Pistachio Investigation Institute, Gaziantep, for providing

the data about the Antep pistachio (Pistacia vera L.).

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